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Programming asynchronous replication in stem cells.

Hagit Masika1, Marganit Farago1, Merav Hecht1

  • 1Department of Developmental Biology and Cancer Research, Hebrew University Medical School, Jerusalem, Israel.

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|November 14, 2017
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Summary
This summary is machine-generated.

Stem cells program allele-specific replication, with the paternal allele consistently replicating early in development. This programmed switching establishes allelic discrimination and diversity across the organism.

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Area of Science:

  • Genomics
  • Developmental Biology
  • Epigenetics

Background:

  • Genomic regions often replicate asynchronously and are expressed monoallelically.
  • The developmental mechanisms establishing these patterns, particularly allele choice during replication, remain largely unknown.

Purpose of the Study:

  • To investigate how asynchronous replication and monoallelic expression patterns are established during development.
  • To determine the role of DNA replication timing in allele selection and the generation of allelic diversity.

Main Methods:

  • Comparative analysis of replication patterns in somatic cells versus embryonic and adult stem cells.
  • Utilizing ground-state embryonic stem (ES) cells to study the initial transition to asynchronous replication.

Main Results:

  • Unlike somatic cells, stem cells exhibit programmed replication switching, generating daughter cells with distinct paternal allele replication timing.
  • In the initial transition to asynchronous replication in ES cells, the paternal allele is consistently selected for early replication.

Conclusions:

  • Allele choice during early development is directed by pre-existing gametic DNA markers.
  • This programmed replication switching is a fundamental strategy for establishing allelic discrimination and generating organism-wide allelic diversity.